After viewing Thole in the 2009 spring training, Mets pitching coach Dan Warthen "gushed" about Thole's catcher skills.[1] In 2009, Thole stated, "My throwing is still coming along."[2] On August 31, 2009, Thole was called up to the major leagues.[3] In his first major league at-bat, he singled to record his first major league hit.

After spending much of the 2010 season in Triple-A Buffalo, Thole was called up to the Mets in June.[4] On July 20, 2010, Thole hit his first major league home run, a solo homer, off of Barry Enright in a game against the Arizona Diamondbacks at Chase Field to give the Mets their first run of the game (3-1).[5] They would lose that game 3-2.[5] On October 1, 2010, he hit a walk-off home run off Tyler Clippard to give the Mets a 2-1 win.[6]

Thole spent the entire season with the New York Mets as a catcher. He hit .268, drove in 40 runs and hit 3 home runs over 340 at bats.

Thole broke camp with the Mets as their starting catcher. On May 9, 2012, Thole was placed on the seven-day disabled list after suffering a concussion in a plate collision with Phillies first baseman Ty Wigginton on May 7.[7] On June 1, 2012, Thole was reactivated and caught Johan Santana's no-hitter; becoming the first Mets catcher to participate in a no-hitter.

On December 17, 2012, the Mets traded Thole, R.A. Dickey, and Mike Nickeas to the Toronto Blue Jays for Travis d'Arnaud, Noah Syndergaard, John Buck, and Wuilmer Becerra.[8] On January 18, 2013, the Blue Jays announced that arbitration with Thole had been avoided by signing him to a two-year contract worth $2.5 million, with a club option for the 2015 season at $1.75 million.[9] On March 24, Thole was reassigned to minor league camp and started the season with the Triple-A Buffalo Bisons.[10] He was recalled by the Blue Jays on June 7 when Henry Blanco was designated for assignment.[11] Thole made his Blue Jays debut in the 16th inning of an 18 inning win against the Texas Rangers on June 8, going 0-2 at the plate. He finished the 2013 season batting just .175 with 1 home run and 8 RBI in 45 games.[12] Thole began the 2014 season in Toronto, as R.A. Dickey's personal catcher. He improved upon his results from 2013, finishing 2014 with a batting average of .252 with 7 RBI in 56 games played.[12] On November 1, the Blue Jays picked up Thole's $1.75 million option for the 2015 season.[13] After the signing of Russell Martin in the offseason, the Blue Jays entered 2015 spring training with 3 catchers on their roster. Martin began catching R.A. Dickey early in camp, and supplanted Thole as his personal catcher. On March 31, Thole was assigned to Triple-A Buffalo.[14]